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2012 Grants - Seyfried

Early Changes in the Brain Proteome and Alzheimer's Disease Risk

Nicholas Seyfried, Ph.D.
Emory University
Atlanta, Georgia

2012 New Investigator Research Grant

Alzheimer's disease is a progressive disorder that begins long before clinical symptoms appear. Past research has found that the asymptomatic (no symptoms) phase of Alzheimer's is linked to abnormal brain accumulations of the protein fragment beta-amyloid and the protein tau in the brain. Yet current studies suggest that other mechanisms are involved in initiating the disease process.

Nicholas Seyfried, Ph.D., and colleagues hypothesize that protein changes in the brain's synapses may play a key role in Alzheimer's onset. Synapses are tiny channels through which brain cells send and receive chemical messages, and synaptic damage can lead to cognitive loss. Such damage is also among the earliest forms of Alzheimer's brain changes. In preliminary experiments, Dr. Seyfried's team has been using a novel form of mass spectrometry (an instrument to identify unknown molecules) to identify thousands of proteins from the autopsied brains of healthy people, people with asymptomatic Alzheimer's disease and people with fully developed Alzheimer's. Mass spectrometry is an analytical method in which proteins and other molecules become ionized—or electrically charged. Once ionized, the proteins can be more easily detected and analyzed in the laboratory.

For their current project, the researchers will employ their mass spectrometry technique to conduct a search for human synaptic proteins that may be linked to early Alzheimer's. Their project's brain samples will be obtained from two large, long-term studies of aging and dementia. Once candidate proteins are identified, Dr. Seyfried's group will determine how they may be associated with genetic and other risk factors for dementia. The results of this work could shed new light on how synaptic changes promote the development of Alzheimer's. They could also suggest novel Alzheimer's therapies that target synaptic protein biomarkers.